DESCRIPTION: (Applicant's Abstract) In the preceding grant periods (87-90, 90-94, 94-97) the mechanisms of pain relief by electro-acupuncture (EA) were extensively studied in animal models. The same approaches with newly developed technologies will be used in the upcoming studies. The first aim is to construct new model of chronic pain in the rat which would be closer to clinical arthritis and causes less suffering for the animal, so that it can be used for the searching of optimal parameters of EA. In addition, since multiple EA sessions are usually needed, it is important to know the optimal time intervals one should take between two EA treatments. The second aim is to study the factors affecting the efficacy of EA-induced analgesia. It has been shown that the effect of EA is determined by a balance between opioid- and the anti-opioid peptides (notably the small peptide CCK-8) in the central nervous system (CNS). It is important to learn if there are other and-opioid peptides existing in the CNS. In 1995, a novel peptide entitled orphan in FQ (OFQ) was characterized from the rat brain. While there is controversy as to whether this peptide works pro or against traditional opioids, findings obtained in this lab, which was reported in 1996 INRC pointed clearly that this is a new antiopioid peptide, at least in the brain of the rat. A series of studies will be performed to compare this new peptide with the well known anti-opioid peptide CCK-8, for which we have spent more than a decade to study its mechanisms of action. It is expected that elucidation of the role played by OFQ in pain and analgesia will open new insight into understanding the mechanisms governing the control of pain and analgesia in normal life and in patients suffering from severe pain. The third aim is to study the genetic factors determining the efficacy of EA analgesia, especially, to answer the question why EA works for some patients (the responders) and not for others (non-responders). Newly developed molecular genetic techniques including the gene knockout mouse will be used, and ways to change non-responders of EA into responders will be evaluated. In summary, "closer to clinical acupuncture practice and deeper to genetic level" will continue to be the theme of this proposal, in order to meet the challenge of an increasing expectation of using alternative medicine in health care and medical sciences.